Three decades after the emergence of HIV there is still no vaccine, and AIDS remains a threat to global public health. However, some HIV-infected individuals eventually develop broadly neutralizing antibodies (bNAbs), i.e., antibodies that neutralize a large panel of HIV viruses and that can delay viral rebound in HIV patients. Such antibodies are relevant to vaccine development, as evidenced by the prevention of infection observed after passive transfer to macaques.
The NIH45-46 antibody that was isolated in a screen using single cell cloning techniques (Scheid et al., 2009, J Immunol Methods 343:65-67; Scheid et al., 2011, Science 333:1633-1637, the entire contents of both of which are herein incorporated by reference), is a more potent clonal variant of VRC01, bNAb directed against the CD4 binding site (CD4bs) of gp120 (Wu et al., 2010, Science 329:856-861; and Zhou et al., 2010, Science 329:811-817, the entire contents of both of which are herein incorporated by reference). Enhancing the efficacy of bNAbs, and in particular, designing bNAbs that retain potency against escape mutants selected during exposure to bNAbs, would facilitate their use as therapeutics.